Mesial Temporal Lobe Epilepsy Related To Hippocampal Sclerosis Research Articles

Anxiety and depressive symptoms long after mesial temporal epilepsy surgery: A prospective study

BackgroundAnxiety and depressive symptoms are prevalent in patients with refractory mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) before and after anterior temporal lobectomy (ATL). Aims(1) To follow the levels of anxiety and depressive symptoms long-term after ATL among patients with refractory MTLE-HS; (2) To identify pre- and postsurgical variables associated with the levels of anxiety and depressive symptoms after surgery. MethodsWe compared the levels of anxiety and depressive symptoms determined by the Hospital Anxiety and Depression Scale (HADS) before and long after ATL (mean 104 months, range 70–130) in 41 consecutive patients refractory MTLE-HS. The last follow-up was between September 2018 and March 2020. We also determined pre- and postsurgical variables independently associated with the HADS scores after surgery. ResultsThe scores of HADS and its subdomains related to anxiety and depression decreased significantly (p < 0.01) after ATL. After multiple linear regressions, the HADS-Anxiety scores before surgery (B = 0.47, CI 95% 0.20 to 0.75, p = 0.001) and at follow-up after surgery (B = 0.07, CI 0.00 to 0.14, p = 0.05) remain independently and positively associated with HADS-Anxiety scores after surgery. The HADS-Depression scores after surgery were independently positively associated with HADS-Depression scores before surgery (B = 0.39, CI 95% 0.10 to 0.76, p = 0.01) and worse seizure control after surgery (B = 1.55, CI 95% 0.23 to 2.87, p = 0.02). ConclusionAnxiety and depressive symptoms in patients with MTLE-HS significantly improved after ATL. Presurgical levels of anxiety and depressive symptoms, respectively, were positively associated with the postsurgical levels of those symptoms. Length of follow-up is associated with anxiety, and worse seizure control is associated with depressive symptoms after ATL. The results have implications for the surgical management of MTLE-HS patients.

Revisiting personality in epilepsy: Differentiation of personality in two epilepsies starting in adolescence

PurposeThe purpose of this study was to investigate personality characteristics and clinical parameters in two well-defined epilepsies: mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE/HS) and juvenile myoclonic epilepsy (JME) through NEO Revised Personality Inventory (NEO-PI-R) and Neurobehavior Inventory (NBI) standardized instruments. MethodsOne hundred patients undergoing corticoamygdalohippocampectomy (CAH), 100 patients with JME, and 100 control subjects answered the personality measures. Clinical parameters such as psychiatric symptoms, seizure frequency, duration of epilepsy, and side of the lesion in MTLE/HS group were investigated. Statistical analysis consisted of the mean and standard deviation (SD) of each variable. Student's t-test or Fisher exact test were used according to the variable studied. ResultsThe three groups were within the average range of NEO-PI-R and NBI, although ‘tendencies’ and differences were demonstrated. The MTLE/HS and control subjects had a similar profile: low scores in Neuroticism and high in Conscientiousness (r = −0.330; p < 0.001/r = −0.567; p < 0.001, respectively) in opposition to what occurred in JME, low in Conscientiousness and high in Neuroticism (r = −0.509; p = 0.005). The NBI ‘sense of personal destiny’ trait was higher (3.15; p = 0.003) in MTLE/HS than in JME and controls. The JME ‘law and order’ scores were lower than in other groups (p = 0.024). A tendency towards specific NBI traits differentiates MTLE/HS (Factor 3) from JME (Factor 1) groups. Psychiatric symptoms and seizure frequency were correlated with worse scores in NBI and, especially, in Neuroticism domain of NEO-PI-R. ConclusionSpecific personality features were linked to each epileptic disease. These findings highlight the importance of considering unique features linked to epilepsy conditions in daily clinical observation to develop support programmes.

Rare variants and de novo variants in mesial temporal lobe epilepsy with hippocampal sclerosis.

ObjectiveWe investigated the role of rare genetic variants and of de novo variants in the pathogenesis of mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS).MethodsWhole-exome sequencing (WES) was performed in patients with MTLE-HS and their unaffected parents (trios). Genes or gene sets that were enriched with predicted damaging rare variants in the patients as compared to population controls were identified. Patients and their parents were compared to identify whether the variants were de novo or inherited.ResultsAfter quality control, WES data from 47 patients (26 female), including 23 complete trios, were available for analysis. Compared with population controls, significant enrichment of rare variants was observed in SEC24B. Integration of gene set data describing neuronal functions and psychiatric disorders showed enrichment signal on fragile X mental retardation protein (FMRP) targets. Twenty-one de novo variants were identified, with many known to cause neuropsychiatric disorders. The FMRP-targeted genes also carried more de novo variants. Inherited compound heterozygous and homozygous variants were identified.ConclusionsThe genetic architecture underlying MTHE-HS is complex. Multiple genes carrying de novo variants and rare variants among FMRP targets were identified, suggesting a pathogenic role. MTLE-HS and other neuropsychiatric disorders may have shared biology.

Predictors of meaningful improvement in quality of life after temporal lobe epilepsy surgery: A prospective study.

To investigate prospectively the independent predictors of a minimum clinically important change (MCIC) in quality of life (QOL) after anterior temporal lobectomy (ATL) for drug-resistant mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) in Brazilian patients. Multiple binary logistic regression analysis was performed to identify the clinical, demographic, radiologic, and electrophysiologic variables independently associated with MCIC in the Quality of Life in Epilepsy-31 Inventory (QOLIE-31) overall score 1year after ATL in 77 consecutive patients with unilateral MTLE-HS. The overall QOLIE-31 score and all its subscale scores increased significantly (p<0.0001) 1year after ATL. In the final logistic regression model, absence of presurgical diagnosis of depression (adjusted odds ratio [OR] 4.4, 95% confidence interval [CI] 1.1-16.1, p=0.02) and a complete postoperative seizure control (adjusted OR 4.1, 95% CI 1.2-14.5, p=0.03) were independently associated with improvement equal to or greater than the MCIC in QOL after ATL. The overall model accuracy for MCIC improvement in the QOL was 85.6%, with a 95.2% of sensitivity and 46.7% of specificity. These results in Brazilian patients reinforce the external validation of previous findings in Canadian patients showing that presurgical depression and complete seizure control after surgery are independent predictors for meaningful improvement in QOL after ATL, and have implications for the surgical management of MTLE patients.

Prnp gene and cerebellum volume in patients with refractory mesial temporal lobe epilepsy

The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of the Prnp was associated with decreased brain volume in healthy volunteers and schizophrenic patients. We investigate the association between the cerebellum volume and the presence of variant allele Valine at codon 129 of the Prnp gene in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). The Prnp coding sequence was determined in 41 refractory MTLE-HS patients. The cerebellum volume corrected by the intracranial volume of patients with the normal Prnp genotypes was compared with that of patients presenting the variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16 showed Met129Val, and 5 had Val129Val. There were no association among clinical, demographic, electrophysiological, antiepileptic drugs used, and the presence of the Prnp variant alleles. The presence of Prnp variant allele at codon 129 was not associated with the analyzed cerebellum volume. Prnp variant alleles at codon 129 are not associated with cerebellum volume in patients with refractory MTLE-HS.

Clinical phenotypes within non-surgical patients with mesial temporal lobe epilepsy caused by hippocampal sclerosis based on response to antiepileptic drugs

PurposeTo evaluate evolution and elucidate clinical phenotypes related to prognosis of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) treated exclusively with antiepileptic drugs (AED). MethodsForty-seven out of 68 MTLE-HS patients treated between January 2005 and June 2010 were retrospectively studied for demographic, clinical and outcome data. The population was divided into drug-responder and drug-resistant patients; the latter was divided, according to the duration of the seizure-free periods along their evolution, into patients with at least one seizure-free period longer than one year and those with shorter periods. Variables were compared between drug-responders vs drug-resistants and drug-resistants with long seizure-free periods vs drug-resistants without it. ResultsThere were 7 (15%) drug-responders, 39 (83%) drug-resistants and 1 patient (2%) with an undetermined response. Eighteen (46%) drug-resistant individuals had seizure-free periods longer than one year, with mean duration of 46 months (3.8 years). Since no factor was statistically associated with long seizure-free period within drug-resistants, we can clinically distinguish two phenotypes: women with left HS and late onset of seizures, with poor prognosis, and men with right HS and earlier appearance of seizures, attaining a better outcome. Twenty out of 47 (42.5%) patients followed an intermittent pattern of epilepsy. ConclusionsNon-surgical MTLE-HS drug-resistant patients can achieve long seizure-free periods with AED, but relapses are common. Female gender, left or bilateral lesion and later onset of seizures seem to be bad prognosis factors within MTLE-HS drug-resistant patients.

Predictors of quality of life in patients with refractory mesial temporal lobe epilepsy

PurposeThe identification of variables associated with health-related quality of life (HRQoL) in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) would improve surgical decision-making and post-operatory follow-up in this group of patients. MethodsWe analyzed the independent association between the Quality of Life in Epilepsy Inventory—31 (QOLIE-31) of 81 consecutive patients with refractory MTLE-HS. The clinical, demographic, radiological and electrophysiological variables were analyzed by multiple linear regression analysis. Key findingsApproximately 36% (adjusted R2=0.36; R coefficient=0.66) of the QOLIE-31 overall score variance was explained by the history of initial precipitant injury, family history of epilepsy, disease duration, age of epilepsy onset, seizure frequency and presence of psychiatric axis-II diagnosis. The variance of QOLIE‐31 sub-scales was: seizure worry=7%; overall QOL=11%; emotional well‐being=32%; energy/fatigue=38%; cognitive function=13%; medication effects=7%; social function=13% (R coefficient between 0.30 and 0.65). SignificanceThe pre-surgical variables studied had relatively low prediction capacity for the overall QOLIE-31 score and its sub-scales in this set of Brazilian patients with refractory MTLE‐HS.

Glucose-dependent insulinotropic peptide receptor expression in the hippocampus and neocortex of mesial temporal lobe epilepsy patients and rats undergoing pilocarpine induced status epilepticus

The glucose-dependent insulinotropic peptide receptor (GIPR) has been implicated with neuroplasticity and may be related to epilepsy. GIPR expression was analyzed by immunohistochemistry in the hippocampus (HIP) and neocortex (Cx) of rats undergoing pilocarpine induced status epilepticus (Pilo-SE), and in three young male patients with left mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) treated surgically. A combined GIPR immunohistochemistry and Fluoro-Jade staining was carried out to investigate the association between the GIPR expression and neuronal degeneration induced by Pilo-SE. GIPR was expressed in the cytoplasm of neurons from the HIP CA subfields, dentate gyrus (DG) and Cx of animals and human samples. The GIPR expression after the Pilo-SE induction increases significantly in the HIP after 1 h and 5 days, but not after 12 h or 50 days. In the Cx, the GIPR expression increases after 1 h, 12 h and 5 days, but not 50 days after the Pilo-SE. The expression of GIPR 12 h after Pilo-SE was inversely proportional to the Fluoro-Jade staining intensity. In the human tissue, GIPR expression patterns were similar to those observed in chronic Pilo-SE animals. No Fluoro-Jade stained cells were observed in the human sample. GIPR is expressed in human HIP and Cx. There was a time and region dependent increase of GIPR expression in the HIP and Cx after Pilo-SE that was inversely associated to neuronal degeneration.

Surgical outcome of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis

Seizure outcome in mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) that was evaluated according to a noninvasive protocol was assessed in 165 patients and reported using both Engel's and ILAE classifications. The mean postoperative follow-up was 5.0 +/- 2.7 years. At the end of first year, 77.1% of patients were in Engel-I, and 52.7% were in ILAE-I. Antiepileptic drugs (AEDs) were discontinued in 41 patients (42.7%), all remained seizure-free for >or= 2 years that could be accepted as "cure." Thirty-six patients had recurrences, 19 had running-down phenomena. Anterior temporal lobectomy (ATL) was performed in 27 patients with a better outcome when compared to patients operated by selective anterior hippocampectomy. Clinical risk factors for better and worse outcome, which show some similarity in different reports, seem to veil the main reason, which is the accurate delineation of epileptogenic zone considering the presence of different subgroups and underlying developmental pathologies.

Cognitive performance of patients with mesial temporal lobe epilepsy is not associated with human prion protein gene variant allele at codons 129 and 171

Cognitive impairment has long been recognized in people with medically refractory epilepsies. Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS), the most common surgically remediable epileptic syndrome, has been associated with a cellular prion protein (PrPc) gene ( Prnp) variant allele at codon 171. The polymorphism consisting of a methionine-for-valine substitution at codon 129 has been associated with early cognitive deterioration in elderly people and patients with Down syndrome. The same variant allele in homozygosis (V129V) has been associated to a lower long-term memory in healthy humans. PrPc mediates several processes related to neuroplasticity, and its role in cognitive processes remains unknown. In this study, we evaluated the genetic contribution of Prnp alleles to cognitive performance in patients with MTLE-HS. Cognitive performance, measured with 19 neuropsychological tests, of patients with refractory MTLE-HS with the normal Prnp genotypes was compared with that of patients with the variant alleles at codons 129 and 171. With the effects of clinical, demographic, electrophysiological, and neuroimaging variable interactions controlled by multiple linear regression analysis and adjustment for multiple test comparisons, the presence of Prnp variant alleles was found not to be significantly associated to cognitive performance of patients with MTLE-HS. The presence of variant alleles at codons 129 and 171 is not associated to cognitive performance of patients with refractory MTLE-HS.

Cognitive performance of patients with mesial temporal lobe epilepsy and incidental calcified neurocysticercosis

Objectives: Although chronic calcified neurocysticercosis (NCC) has been considered a major cause of symptomatic epilepsy in developing countries, it can also be an incidental pathological finding in epileptic patients from...

Interictal SPECT in patients with mesial temporal lobe epilepsy and psychosis: a case-control study

Psychosis is commonly observed in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). Interictal single photon emission computed tomography (SPECT) was performed to compare regional cerebral blood flow (rCBF) pattern of MTLE-HS patients with psychosis of epilepsy (POE) comorbidity and MTLE-HS patients without any psychiatric disorders (Control group). For this, 21 patients with POE and 23 Control patients were matched by educational level, clinical, demographic, electrophysiological, and MRI data. SPECT scans were acquired using 99mTc and interpreted with a semiquantitative method. We analyzed brain regions of interest (ROI) of frontal, temporal, and parietal cortex, in addition to subcortical structures. There were no significant statistical differences of ROI between the POE group and the Control group after Bonferroni adjustment. However, we observed a trend for rCBF increase of right posterior cingulate in the POE Group. This increase would be in accordance with recent findings of cingulate abnormalities in schizophrenia, suggesting that abnormal function in this region might be associated with the psychotic phenomena.

High capacity and low cost detection of prion protein gene variant alleles by denaturing HPLC

Mutations in the human prion protein gene ( PRNP) are responsible for hereditary diseases called transmissible spongiform encephalopathies (TSE) and a polymorphic site at codon 129 determines sensitivity to infectious forms of these maladies. More recently, codon 129 has been related to cognition performance in the elderly, in Alzheimer disease (AD) and in Down syndrome. Furthermore, a rare polymorphism at codon 171 was described in 23% of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS), the most common form of surgically remediable epileptic syndrome. Thus, a method that permits fast and efficient screening of PRNP mutations and polymorphisms in patients, in high risk populations, and in family members is desirable. In the present study, we established the conditions for analysis of the PRNP open reading frame using denaturing high-performance liquid chromatography (DHPLC), whereby unpurified PCR products were subjected to denaturing and reannealing steps leading to heteroduplex formation. We described specific profiles for the PRNP polymorphisms at codons 129 (M/V), 117 (A/A silent), 219 (E/K), 171 (N/S), and the octarepeat deletion using amplified DNA from 562 samples. The chromatograms for TSE-associated mutations at codons 102 (P/L), 183 (T/A), and 210 (V/I) were also determined. Specificity of the DHPLC profile for each PRNP variant allele was confirmed in 100% of the samples by direct and cloned DNA sequencing in addition to endonuclease digestion when applicable. Therefore, the present study shows that DHPLC is a rapid, highly accurate and efficient technique for the detection of PRNP genetic variants.